目的:探究白细胞介素(interleukin,IL)-33、高迁移率族蛋白B1(high mobility group protein B1,HMGB1)、microRNA-122在脓毒症中的表达及意义。方法:选取2016年5月至2018年5月于上海市第六人民医院金山分院接受治疗的脓毒症患者60例,并...目的:探究白细胞介素(interleukin,IL)-33、高迁移率族蛋白B1(high mobility group protein B1,HMGB1)、microRNA-122在脓毒症中的表达及意义。方法:选取2016年5月至2018年5月于上海市第六人民医院金山分院接受治疗的脓毒症患者60例,并根据患者脓毒症严重程度分为脓毒症组(32例)和重症脓毒症组(28例),随机选取同期于我院进行体检的健康人作为对照组(30例)。抽取三组研究对象清晨空腹静脉血5 mL并进行离心处理,酶联免疫吸附试验法(enzyme linked immunosorbent assay,ELISA)检测IL-33水平,免疫透射比浊法检测HMGB1水平,Western blot法检测microRNA-122表达,并对IL-33、HMGB1、microRNA-122在脓毒症中相关性进行研究。结果:脓毒症组和重症脓毒症组患者血清IL-33、HMGB1表达水平和microRNA-122相对表达量较正常对照组明显升高,差异具有统计学意义(F值分别为36.39,22.06和56.43,P值均<0.05)。重症脓毒症患者血清IL-33、HMGB1表达水平和microRNA-122相对表达量明显高于脓毒症患者,差异具有统计学意义[(14.87±2.03)pg/mL比(12.66±1.97)pg/mL,(137.69±24.51)μg/L比(80.66±12.97)μg/L,(1.63±0.08)比(1.35±0.05),t值分别为4.27,11.46和16.47,P值均<0.05)]。对IL-33、HMGB1、microRNA-122在脓毒症中表达进行相关分析,结果显示IL-33与HMGB1,IL-33与microRNA-122,HMGB1与microRNA-122表达水平变化均呈正相关(r值分别为0.73、0.76、0.59,P值均<0.05)。结论:IL-33、HMGB1、microRNA-122在脓毒症中表达异常,并且三者之间具有一定相关性,对IL-33、HMGB1、microRNA-122表达水平进行检测能够为脓毒症患者疾病严重程度的临床诊断提供一定的帮助。展开更多
Innate immunity plays a prominent role in the host defense against pathogens and must be precisely regulated.As vital orchestrators in cholesterol homeostasis,microRNA-33/33*have been widely investigated in cellular m...Innate immunity plays a prominent role in the host defense against pathogens and must be precisely regulated.As vital orchestrators in cholesterol homeostasis,microRNA-33/33*have been widely investigated in cellular metabolism.However,their role in antiviral innate immunity is largely unknown.Here,we report that VSV stimulation decreased the expression of miR-33/33*through an IFNAR-dependent manner in macrophages.Overexpression of miR-33/33*resulted in impaired RIG-I signaling,enhancing viral load and lethality whereas attenuating type I interferon production both in vitro and in vivo.In addition,miR-33/33*specifically prevented the mitochondrial adaptor mitochondrial antiviral-signaling protein(MAVS)from forming activated aggregates by targeting adenosine monophosphate activated protein kinase(AMPK),subsequently impeding the mitophagy-mediated elimination of damaged mitochondria and disturbing mitochondrial homeostasis which is indispensable for efficient MAVS activation.Our findings establish miR-33/33*as negative modulators of the RNA virus-triggered innate immune response and identify a previously unknown regulatory mechanism linking mitochondrial homeostasis with antiviral signaling pathways.展开更多
文摘目的:探究白细胞介素(interleukin,IL)-33、高迁移率族蛋白B1(high mobility group protein B1,HMGB1)、microRNA-122在脓毒症中的表达及意义。方法:选取2016年5月至2018年5月于上海市第六人民医院金山分院接受治疗的脓毒症患者60例,并根据患者脓毒症严重程度分为脓毒症组(32例)和重症脓毒症组(28例),随机选取同期于我院进行体检的健康人作为对照组(30例)。抽取三组研究对象清晨空腹静脉血5 mL并进行离心处理,酶联免疫吸附试验法(enzyme linked immunosorbent assay,ELISA)检测IL-33水平,免疫透射比浊法检测HMGB1水平,Western blot法检测microRNA-122表达,并对IL-33、HMGB1、microRNA-122在脓毒症中相关性进行研究。结果:脓毒症组和重症脓毒症组患者血清IL-33、HMGB1表达水平和microRNA-122相对表达量较正常对照组明显升高,差异具有统计学意义(F值分别为36.39,22.06和56.43,P值均<0.05)。重症脓毒症患者血清IL-33、HMGB1表达水平和microRNA-122相对表达量明显高于脓毒症患者,差异具有统计学意义[(14.87±2.03)pg/mL比(12.66±1.97)pg/mL,(137.69±24.51)μg/L比(80.66±12.97)μg/L,(1.63±0.08)比(1.35±0.05),t值分别为4.27,11.46和16.47,P值均<0.05)]。对IL-33、HMGB1、microRNA-122在脓毒症中表达进行相关分析,结果显示IL-33与HMGB1,IL-33与microRNA-122,HMGB1与microRNA-122表达水平变化均呈正相关(r值分别为0.73、0.76、0.59,P值均<0.05)。结论:IL-33、HMGB1、microRNA-122在脓毒症中表达异常,并且三者之间具有一定相关性,对IL-33、HMGB1、microRNA-122表达水平进行检测能够为脓毒症患者疾病严重程度的临床诊断提供一定的帮助。
基金supported by the National Natural Science Foundation of China(81401283,81771699)Zhejiang Provincial Natural Science Foundation of China(LZ19H100001,LY18H100004,and LY15C080001)Fundamental Research Funds for the Central Universities(2018QNA7008).
文摘Innate immunity plays a prominent role in the host defense against pathogens and must be precisely regulated.As vital orchestrators in cholesterol homeostasis,microRNA-33/33*have been widely investigated in cellular metabolism.However,their role in antiviral innate immunity is largely unknown.Here,we report that VSV stimulation decreased the expression of miR-33/33*through an IFNAR-dependent manner in macrophages.Overexpression of miR-33/33*resulted in impaired RIG-I signaling,enhancing viral load and lethality whereas attenuating type I interferon production both in vitro and in vivo.In addition,miR-33/33*specifically prevented the mitochondrial adaptor mitochondrial antiviral-signaling protein(MAVS)from forming activated aggregates by targeting adenosine monophosphate activated protein kinase(AMPK),subsequently impeding the mitophagy-mediated elimination of damaged mitochondria and disturbing mitochondrial homeostasis which is indispensable for efficient MAVS activation.Our findings establish miR-33/33*as negative modulators of the RNA virus-triggered innate immune response and identify a previously unknown regulatory mechanism linking mitochondrial homeostasis with antiviral signaling pathways.
